The past 40 years has witnessed an epidemic of childhood and adult obesity, attributed in part to programming effects of the in utero environment. During this time period, the use of plastics (e.g., water bottles, food can liners) containing bisphenol A (BPA) has accelerated in parallel to obesity rates. BPA, an endocrine disruptor (EDC) chemical, is ubiquitous with significant levels in pregnant women, fetal plasma and amniotic fluid. Using a clinically relevant rat model of maternal BPA-exposure during pregnancy and lactation we have demonstrated that BPA increases offspring body weights, adiposity and adipocyte progenitor cell proliferation and lipid storage. However, the mechanisms by which BPA exerts its effects on adiposity are unknown. The underlying cause of BPA-programmed obesity may be attributed to BPA effects on glucocorticoid pathways, specifically through activation of the hypothamalic-pituitary-adrenal (HPA) axis and/or increased adipose tissue-specific glucocorticoid exposure. The proposed studies will determine basal and stimulated functioning of the HPA axis in control and BPA-treated offspring. Since BPA-programmed increases in adipocyte proliferation and lipid storage may also be due to the effects of local adipose tissue glucocorticoid exposure, we will further address the gene and protein expression of the enzyme 11hydroxysteroid dehydrogenase, which converts inactive ketoglucocorticoids to active 11-hydroxyglucocorticoids, thereby regulating activation of the glucocorticoid receptor at the adipose tissue level. The studies will utilize BPA-offspring at birt (P1), at weaning (P21) and in adulthood (6 months) to first determine the effects of BPA-exposure during pregnancy and lactation on offspring glucocorticoid homeostasis, and second to determine whether BPA-increased glucocorticoid exposure persists into adulthood. In view of the dramatic increase in obesity, especially in children, understanding the mechanisms underlying how perinatal BPA exposure contributes to the etiology of obesity is essential to the development of effective strategies for the prevention and treatment of the global obesity epidemic.